Absence Of Cerebral Blood Flow Research Articles

Cerebral Perfusion and Neuromonitoring during Complex Aortic Arch Surgery: A Narrative Review.

Complex ascending and aortic arch surgery requires the implementation of different cerebral protection strategies to avoid or limit the probability of intraoperative brain damage during circulatory arrest. The etiology of the damage is multifactorial, involving cerebral embolism, hypoperfusion, hypoxia and inflammatory response. These protective strategies include the use of deep or moderate hypothermia to reduce the cerebral oxygen consumption, allowing the toleration of a variable period of absence of cerebral blood flow, and the use of different cerebral perfusion techniques, both anterograde and retrograde, on top of hypothermia, to avoid any period of intraoperative brain ischemia. In this narrative review, the pathophysiology of cerebral damage during aortic surgery is described. The different options for brain protection, including hypothermia, anterograde or retrograde cerebral perfusion, are also analyzed, with a critical review of the advantages and limitations under a technical point of view. Finally, the current systems of intraoperative brain monitoring are also discussed.

Neurologic recovery after ten minutes of absent cerebral blood flow at normothermia.

Prolonged normothermic cardiac arrest is associated with a high incidence of neurological morbidity and mortality. Whole body temperature-controlled perfusion has been applied to limit reperfusion injury and minimize ischemia. We describe the full recovery of a patient after the application of rapid hypothermia following an intraoperative aortic rupture with ten minutes of absent cerebral blood flow.

Transcranial Doppler and Magnetic Resonance in Tanzanian Children With Sickle Cell Disease.

Background and Purpose- We determined prevalences of neurological complications, vascular abnormality, and infarction in Tanzanian children with sickle cell disease. Methods- Children with sickle cell disease were consecutively enrolled for transcranial Doppler; those with slightly elevated (>150 cm/s), low (<50 cm/s) or absent cerebral blood flow velocity (CBFv) were invited for brain magnetic resonance imaging and magnetic resonance angiography. Results- Of 200 children (median age 9; range 6-13 years; 105 [2.5%] boys), 21 (11%) and 15 (8%) had previous seizures and unilateral weakness, respectively. Twenty-eight (14%) had elevated and 39 (20%) had low/absent CBFv, all associated with lower hemoglobin level, but not higher indirect bilirubin level. On multivariable analysis, CBFv>150 cm/s was associated with frequent painful crises and low hemoglobin level. Absent/low CBFv was associated with low hemoglobin level and history of unilateral weakness. In 49 out of 67 children with low/absent/elevated transcranial Doppler undergoing magnetic resonance imaging, 43% had infarction, whereas 24 out of 48 (50%) magnetic resonance angiographies were abnormal. One had hemorrhagic infarction; none had microbleeds. Posterior circulation infarcts occurred in 14%. Of 11 children with previous seizure undergoing magnetic resonance imaging, 10 (91%) had infarction (5 silent) compared with 11 out of 38 (29%) of the remainder ( P=0.003). Of 7 children with clinical stroke, 2 had recurrent stroke and 3 died; 4 out of 5 had absent CBFv. Of 193 without stroke, 1 died and 1 had a stroke; both had absent CBFv. Conclusions- In one-third of Tanzanian children with sickle cell disease, CBFv is outside the normal range, associated with frequent painful crises and low hemoglobin level, but not hemolysis. Half have abnormal magnetic resonance angiography. African children with sickle cell disease should be evaluated with transcranial Doppler; those with low/absent/elevated CBFv should undergo magnetic resonance imaging/magnetic resonance angiography.

Abstract WP400: Magnetic Resonance-Derived Oxygen Extraction Fraction in White Matter Hyperintensities Compared to Normal Appearing White Matter

Introduction: White matter hyperintensities (WMH), a common neuroradiological feature seen with aging, increases the risk of stroke, dementia, disability and mortality. The underlying pathophysiology leading to WMH is incompletely understood. Here, we examined the role of regional cerebral blood flow (CBF) and oxygen extraction fraction (OEF) in WMH. Methods: Subjects with WMH (n=9) and age-matched controls (n=9) were imaged in a 3T MRI Scanner. OEF was obtained using an asymmetric spin echo sequence while CBF was obtained with pseudo-continuous arterial spin labeling. WMH were graded according to Fazekas et al. For tissue-type quantification, CBF and OEF images were segmented to classify whole brain (WB), gray matter (GM), white matter (WM), white matter hyperintensities (WMH), and normal appearing white matter (NAWM). Results: CBF and OEF in WB, GM and WM did not differ between cohorts. However, differences emerged when comparing the WMH and NAWM segmented tissues. Specifically, CBF in WMH was less than half that seen in NAWM in the WMH group, and similarly lower than normal WM in controls. Moreover, OEF in WMH was higher compared to NAWM and WM in controls, but this did not reach statistical significance (Table). Conclusions: CBF and OEF did not differ between subjects with or without WMH. However, within the WMH group, regions of WMH had significantly lower but not absent CBF and trends towards higher OEF compared to NAWM and normal WM in controls. These data suggest that regions of WMH do not represent irreversibly infarcted tissue, but rather, may be viable tissue under chronic metabolic stress. Increased OEF in WMH may be a marker of salvageable brain tissue; However, additional work is needed to confirm these results.

Pediatric Nuclear Medicine in Acute Care

Various radiopharmaceuticals are available for imaging pediatric patients in an acute care setting. This article focuses on the common applications used on a pediatric patient in acute care. To confirm the clinical diagnosis of brain death, brain scintigraphy is considered accurate and has been favorably compared with other methods of detecting the presence or absence of cerebral blood flow. Ventilation-perfusion lung scans are easy and safe to perform with less radiation exposure than computed tomography pulmonary angiography and remain an appropriate procedure to perform on children with suspected pulmonary embolism as a first imaging test in a hemodynamically stable patient with no history of lung disease and normal chest radiograph. (99m)Tc pertechnetate scintigraphy (Meckel's scan) is the best noninvasive procedure to establish the diagnosis of ectopic gastric mucosa in Meckel's diverticulum. Hepatobiliary scintigraphy is the most accurate diagnostic imaging modality for acute cholecystitis. (99m)Tc-dimercaptosuccinic acid scintigraphy is the simplest, and the most reliable and sensitive method for the early diagnosis of focal or diffuse functional cortical damage. Bone scintigraphy is a sensitive and noninvasive technique for the diagnosis of bone disorders such as osteomyelitis and fracture. Of recent, positron emission tomography imaging using (18)F-NaF has been introduced as an alternative to bone scintigraphy. (18)F-fluorodeoxyglucose-positron emission tomography has the potential to replace other imaging modalities, such as the evaluation of fever of unknown origin in pediatric patients, with better sensitivity and significantly less radiation exposure than gallium scan.

Maintained consciousness during witnessed asystole after spinal anesthesia for Cesarean section

Despite its low incidence, cardiac arrest after spinal anesthesia carries a high mortality. Counterintuitively, young and healthy patients with low resting pulse are at increased risk. We report the case of a healthy 24 yr G 2 P0 at term scheduled for elective Cesarean section whose heart rate decreased to 30 bpm, followed by more than 30 seconds of asystole 3 minutes after spinal anesthesia with a T4 level block. Following atropine and epinephrine administration, the patient had several single heart beats when startled by the anesthesiologist’s loud voice and when touching her chest to prepare for chest compressions. Eventually, regular sinus rhythm returned with a heart rate of up to 160 bpm. The patient was rapidly prepped, and within 5 minutes, the fetus was delivered surgically with Apgar scores of 8 and 9. Most unusually, the patient remained responsive during the entire event and denied having lost consciousness. Supine position and volume loading may have contributed to venous pooling within the cerebral vasculature, so even in the absence of cerebral blood flow during asystole venous blood may still have been present and delayed cerebral hypoxia. Therefore, loss of consciousness in the supine position may occur considerably after the onset of asystole which may reduce the time available for treatment and contribute to its high mortality. Inspiration during the two startle reactions may have decreased vagal tone and permitted enough spontaneous cardiac activity to circulate the resuscitative drugs without CPR.

Maintained consciousness during witnessed asystole after spinal anesthesia for Cesarean section

Despite its low incidence, cardiac arrest after spinal anesthesia carries a high mortality. Counterintuitively, young and healthy patients with low resting pulse are at increased risk. We report the case of a healthy 24 yr G2P0 at term scheduled for elective Cesarean section whose heart rate decreased to 30 bpm, followed by more than 30 seconds of asystole 3 minutes after spinal anesthesia with a T4 level block. Following atropine and epinephrine administration, the patient had several single heart beats when startled by the anesthesiologist’s loud voice and when touching her chest to prepare for chest compressions. Eventually, regular sinus rhythm returned with a heart rate of up to 160 bpm. The patient was rapidly prepped, and within 5 minutes, the fetus was delivered surgically with Apgar scores of 8 and 9. Most unusually, the patient remained responsive during the entire event and denied having lost consciousness. Supine position and volume loading may have contributed to venous pooling within the cerebral vasculature, so even in the absence of cerebral blood flow during asystole venous blood may still have been present and delayed cerebral hypoxia. Therefore, loss of consciousness in the supine position may occur considerably after the onset of asystole which may reduce the time available for treatment and contribute to its high mortality. Inspiration during the two startle reactions may have decreased vagal tone and permitted enough spontaneous cardiac activity to circulate the resuscitative drugs without CPR.

Integrated Cerebral Protection Combined Antegrade and Retrograde Cerebral Perfusion during Deep Hypothermic Circulatory Arrest

Aortic arch surgery requires temporary interruption of cerebral perfusion. Hypothermic circulatory arrest (HCA) is an established method of central nervous system protection for limited periods of absent cerebral blood flow. Adjuncts to increase the safe duration of circulatory arrest include either retrograde cerebral perfusion (RCP) or antegrade cerebral perfusion (ACP), with most complex aortic operations now performed using HCA with ACP. We reasoned that optimal cerebral protection might be achieved with a combination of ACP and RCP (integrated brain protection) and present an early clinical experience that supports this approach. The integrated brain protection strategy included sequential overlapping periods of RCP, ACP, and RCP during HCA. Moderate systemic hypothermia (25°C) was used. Patient data were gathered through retrospective chart review. Between 2008 and 2009, six consecutive patients underwent ascending aortic graft replacement for acute type A dissection using HCA and integrated brain protection. The mean minimum systemic temperature was 22.9 ± 1.8°C, the mean total HCA time was 34 ± 5 minutes, and the mean duration of ACP and RCP was 22 ± 6 and 7 ± 5 minutes, respectively. Patients were awake and followed commands 10.1 ± 3.4 (range, 5-13) hours after operation, and there was no evidence of temporary neurologic dysfunction. There was no operative mortality. Integrated brain protection using both RCP and ACP during HCA is a promising approach for the safe performance of complex aortic surgery and is worthy of evaluation in larger clinical series.

Residual brain viability, evaluated by 99mTc-ECD SPECT, in patients with suspected brain death and with confounding clinical factors

In 1968, the Harvard criteria for brain death diagnosis were introduced in clinical practice. These include no movements or breathing, no reflexes, and flat electroencephalogram in the absence of confounding factors, including hypothermia, drugs, electrolyte, and endocrine disturbances. When confounding factors occur, confirmatory tests documenting the absence of cerebral blood flow, such as cerebral angiogram, transcranial Doppler sonography, computed tomography angiography, and nuclear techniques, are required. The aim of this study was to evaluate the clinical value of single-photon emission computed tomography (SPECT) with technetium-99m (Tc)-ECD in the diagnosis of brain death in a cohort of patients with confounding factors. Fifty-two patients were studied between 1 January 2000 and 23 September 2008. The criteria for the request for Tc-ECD SPECT were sodic thiopental withdrawal after less than 24 h, unreceptivity and unresponsivity of brainstem reflexes, anesthesia in the last 24 h, hypothermia, anamnesis for barbiturate use, electroencephalogram artefacts, toxic state, and pediatric criteria. All patients underwent Tc-ECD SPECT using a dual-headed camera fitted with a high-resolution low-energy collimator. Images were reconstructed and processed according to standard procedures and interpreted qualitatively by two experienced observers. The presence of spots of residual brain viability was observed in 13 patients: 25% of our patient cohort. The patients with residual viability were younger (aged 30.92+/-17.28 years) in comparison with those with no viability (41.91+/-18.77 years, P<0.031). Considering the eligibility for transplantation, there were 12 of 13 patients in the residual viability group and 31 of 39 in the no viability group (P<0.0001). All patients with spots of brain uptake were monitored daily by Tc-ECD SPECT, and all of them reached the condition of empty skull after one or multiple studies. The opposition to organ donation was observed in six of 13 patients with spots of viable brain tissue and in three of 39 with no signs of residual viability (P<0.001). In patients with confounding factors in whom brain death diagnosis is equivocal, Tc-ECD SPECT is a helpful and safe diagnostic approach, allowing a three-dimensional evaluation of cortical and brainstem viability. It guarantees an unequivocal diagnosis of brain death for patients who are potential candidates for organ donation. The persistence of viable spots of brain tissue was found in 25% of our patients and was more frequent in young patients. This affects the opposition to donation.

A Review of Ancillary Tests in Evaluating Brain Death

The neurological determination of death (NDD) is primarily considered to be clinical. However, situations may arise where confounding factors make this clinical assessment difficult or impossible. As a result, ancillary tests have been developed in order to aid in the confirmation of brain death. As assessment of neuronal electrical activity; electroencephalography (EEG) is no longer recommended in this determination, tools assessing cerebral perfusion, as reflected by the presence or absence of cerebral blood flow (CBF), are the mainstay of NDD. The preferred ancillary test currently is Hexamethylpropylene amine oxime-single photon emission computed tomography (HMPAO SPECT) radionuclide angiography. When this is not available, or is equivocal, 4-vessel cerebral angiography can be used to determine the presence or absence of intracranial blood flow. However, as cerebral angiography has its own limitations, other techniques are sought by physicians in the Intensive Care and Neuro-intensive Care settings to replace cerebral angiography. In this article, we briefly review the history of diagnosis of brain death, pathophysiologic issues in making this determination, and currently available CBF imaging techniques, discussing each in turn with respect to their utility in the diagnosis of brain death.

The influence of variations in blood flow on pulsed Doppler ultrasonic heating of the cerebral cortex of the neonatal pig

Pulsed Doppler ultrasound examination of the fetal cerebral circulation may cause potentially harmful temperature elevations in brain tissue immediately beneath the insonated segment of the skull. This study measured the effect of variations in cerebral blood flow on ultrasonic heating of the cerebral cortex of anaesthetised, neonatal pigs. Wide and narrow ultrasound beams were used. Pulsed ultrasound exposures were delivered in 90 s bursts at 5.8 μs pulse length, pulse repetition frequency 8 kHz and centre frequency 3.5 MHz. Studies were performed with the target at the focus of a fixed, stationary beam of 0.3 cm −6 dB beam width (narrow beam) and I spta 1.4 W/cm 2 ( n = 11), or with the target in the near field of a fixed, stationary beam of 1.6 cm −6 dB beam width (wide beam) and I spta 3.6 W/cm 2( n = 5). The 90 s ultrasound exposures were performed under three different conditions of ambient cerebral blood flow: baseline (during normocarbic, normoxic conditions), increased (during hypercarbic, hypoxic conditions) and absent (postmortem). Cerebral blood flow was measured using the radiolabelled microsphere technique. In the narrow beam studies, cerebral blood flow during baseline was 34 ± 4 ml/min/100 g, rising to 109 ± 32 ml/min/100 g during the increased phase ( p < 0.001); in the wide beam studies baseline flows were 29 ± 9 ml/min/100 g, whereas flows in the increased phase were 128 ± 32 ml/min/100 g ( p < 0.001). There was no difference in the heating curves for normal, increased and absent cerebral blood flow for exposure to the narrow beam, when mean temperature increases of 1.5°C at 90 s were recorded in each case ( p > 0.21, power > 0.8). However, the heating curves for the wide beam were significantly different for the three rates of blood flow with mean temperature increases of 1.9°C (normal flow), 1.7°C (increased flow) and 2.4°C (no flow) recorded at 90 s ( p < 0.05).

Evaluation of Brain Death by CT Angiography: Initial Experience

Purpose : The angiographic demonstration of absent cerebral blood flow is presently considered to be the most reliable method of confirming brain death. The purpose of this study is to determine whether CT angiography (CTA) with spiral CT can rapidly and specifically establish a diagnosis of brain death. Materials and Methods : A total of fifteen CT angiograms (brain death, n=9;severe coma, n=6 within 24 hours of the study) were obtained prospectively in 12 patients with an established clinical diagnosis; Two patients underwent repeated CTA. Twenty seconds after beginning the injection of contrast media (100 mL at a rate of 3 mL/sec), CT scanning (30 -second continuous exposure and 60 -mm length) was performed with a table speed of 2 mm/sec and a section thickness of 2 mm. For each case, the presence or absence of opacification of inter-nal carotid arteries (ICA), vertebral and basilar arteries (VBA), anterior cerebral arteries (ACA), middle cerebral arteries (MCA), posterior cerebral arteries (PCA), distal branches of cerebral arteries, and superficial temporal arteries (STA) was ascertained. Results : Except in one clinically brain-dead patient, whose EEG was difficult to interpret due to excessive arti-facts, the distal branches of cerebral arteries did not opacify. STA, on the other hand, was always visible on both sides. In all brain-dead patients but three, the ICA and proximal ACA, MCA, or PCA escaped visualiza-tion. In the remaining three cases with large skull defect or skull fracture, however, CT angiography showed faint opacification of the ICA and proximal segments of cerebral arteries. Cerebral arterial flow was preserved in all six patients in whom there was no clinical evidence of brain death. Conclusion : CTA may be used as a confirmatory test for the determination of brain death.

Rectal-scalp temperature difference predicts brain death in children

When brain death in children occurs, commonly the scalp feels cold despite a normal core temperature. This phenomenon might reflect absent cerebral blood flow and metabolic activity. The authors, therefore, measured rectal-scalp temperature differences in critically ill comatose children to test the hypothesis that a particular temperature difference may correlate with clinical brain death. In a prospective cohort study set in a pediatric intensive care unit, rectal-scalp, rectal-abdomen, and rectal-mastoid temperatures in critically ill comatose children older than 18 months of age were measured before and during brain death evaluations. Twelve children were enrolled. Clinical criteria for brain death were met by seven patients, and five patients survived. All of the seven children who died had rectal-scalp temperature differences greater than 4°C (mean = 6.7, range = 6.0-7.4) at the time of clinical brain death. No survivor had a rectal-scalp temperature difference of 4°C at any time (mean = 3.4, range = 2.9-3.9). Rectal-scalp temperature differences of those who died and those who survived were significantly different at the P < 0.005 level. Rectal-abdomen and rectal-mastoid temperature differences did not correlate with clinical brain death or rectal-scalp temperature difference. In this preliminary study a rectal-scalp temperature difference of greater than 4°C correlates with clinical criteria for brain death in children.

Hypothalamic and Pituitary Function in Brain Death

Hypothalamic and pituitary hormone levels were measured in 56 patients meeting the criteria of brain death proposed by the Japanese Ministry of Welfare. Pituitary hormone releasing tests were carried out in 39 patients. In addition, cerebral angiography and transcranial Doppler (TCD) were performed in 13 and six patients, respectively, just after hormone measurements. Serum hypothalamic and pituitary hormone levels were inconsistently high based on the half life time in the presumed absence of cerebral blood flow shown by angiography. The responses to releasing hormones were normal in 16 patients. TCD detected cerebral blood flow in the middle cerebral artery or ophthalmic artery in three patients who showed non-filling on angiography. Postmortem microscopic examination of the hypothalamus and anterior pituitary lobe revealed normal structure and cells intermingled with lytic changes and necrosis. This series suggests that some part of the hypothalamus and hypophysis may still be alive after brain death, although the function of these regions may be clinically insignificant.

Usefulness of EEG in the evaluation of brain death in children: the pros

The confirmatory tests most frequently used in the evaluation of the cerebral function are cerebral blood flow (CBF) studies and the EEG. Absence of CBF by 4-vessel angiography is considered to be the most reliable test to determine cerebral death but the logistics of obtaining this study preclude its use. The accuracy and reliability of the EEG in the diagnosis of brain death have been frequently questioned (Drake et al. 1986; Vernon and Holtzman 1986) despite the existence of studies

Xenon-enhanced computed tomography in brain death.

The absence of cerebral blood flow is a valuable adjunct confirming clinical criteria of brain death. However, current methods to confirm absent cerebral blood flow have problems that limit their clinical use. We reviewed cerebral blood flow data obtained with xenon-enhanced computed tomography in nine patients who were being evaluated for brain death. In eight patients who met clinical criteria for brain death, mean cerebral blood flow was 1.6 +/- 2.0 mL X 100 g X min. This value was within the range of error inherent in the method, and therefore represented absent flow. In a patient with persistent respiratory efforts, flow values compatible with absent flow were obtained in the supratentorial compartment, while mean flows as high as 24 mL X 100 g X min were measured in selected regions of interest in the infratentorial compartment, correlating with the clinical evidence of residual function of the brain stem. Xenon-enhanced computed tomography may be a useful test to confirm the absence of cerebral blood flow in patients being evaluated for brain death.

Brain death in children: Characteristics common carotid arterial velocity patterns measured with pulsed Doppler ultrasound

The clinical criteria for brain death in children remain controversial. An accepted confirmatory test for brain death is the documented absence of intracranial blood flow, the most common methods being arteriography and radionuclide cerebral angiography. We correlated the common carotid arterial blood velocity patterns measured by pulsed Doppler ultrasound in 32 brain-dead infants and children with results of their clinical examinations and, whenever possible, with radionuclide cerebral angiography. A distinct, characteristic carotid arterial blood velocity waveform indicating absent cerebral blood flow appeared in 19 of the 23 brain-dead patients 4 months of age or older. The velocity patterns of the other four older children were similar, but not identical, to the characteristic waveform. The remaining nine brain-dead patients were infants 4 months of age or younger. These infants had velocity waveforms different from those of healthy infants, but also were totally different from the characteristic brain death pattern of older children. No patient had the characteristic brain death waveform without being clinically brain dead. Measurement of carotid arterial blood velocity with pulsed Doppler ultrasound is a repeatable, noninvasive, portable test useful for confirmation of brain death in children.

Determination of brain death with 123I-IMP and 99mTc-HM-PAO.

Brain imaging with radiolabeled amines, 123I-IMP and 99mTc-HM-PAO, is a rapid, safe, and specific bedside test for confirming brain death in the absence of cerebral blood flow. Therapeutic phenobarbital or thiopental levels do not interfere with the cerebral penetration ability of the lipophilic radiopharmacons.

Diagnosis of Brain Death in Children by Radionuclide Cerebral Imaging

Nine children with clinically suspected brain death were evaluated by radionuclide cerebral imaging and four-vessel dye contrast cerebral arteriography. The scans showing absence of cerebral blood flow were verified by arteriography in all children. There was complete agreement in all cases. It was concluded that failure to detect cerebral blood flow by radionuclide cerebral imaging in children is a valid demonstration of absence of cerebral circulation for purposes of determining brain death. The scan is significantly less expensive than dye-contrast arteriograms. The test is portable, and thus it eliminates the need for transportation of extraordinarily ill patients. The scanning technique is noninvasive and may be particularly helpful in the diagnosis of brain death in patients in whom intravenous infusions of barbiturate might otherwise obscure the clinical and EEG examination.

Failure of electroencephalography to diagnose brain death in comatose children

Two isoelectric electroencephalograms obtained 24 hours apart support a clinical diagnosis of brain death in prolonged coma. Without documentation of electrocerebral silence, physicians are reluctant to discontinue vital support systems. A radionuclide bolus technique has been developed that documents the absence of cerebral blood flow in suspected brain death and supplements the flat EEG. In a recent review of this technique, all 27 adults who had EEG activity maintained the integrity of their cerebral blood flow. This contrasts to our studies of 5 children, all of whom demonstrated persistent EEG activity but had no evidence of cerebral blood flow by either the isotope bolus technique (5 patients) or cerebral angiography (4 patients). These children (mean age, 7 months) lacked cephalic reflexes and were maintained on assisted ventilation for an average of 15 days. Multiple electroencephalographic tracings persistently demonstrated low-voltage cortical activity over this time. Despite the lack of cerebral blood flow, all patients were continued on respiratory support. At autopsy, extensive brain liquefaction necrosis was noted. In comatose children, EEG monitoring may be of limited value while cerebral blood flow measurements can provide more practical and prognostic information.